Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Treatment of Down syndrome in mice restores nerve growth in cerebellum

25.01.2006


Researchers at Johns Hopkins restored the normal growth of specific nerve cells in the cerebellum of mouse models of Down syndrome (DS) that were stunted by this genetic condition. The cerebellum is the rear, lower part of the brain that controls signals from the muscles to coordinate balance and motor learning.



The finding is important, investigators say, because the cells rescued by this treatment represent potential targets for future therapy in human babies with DS. And it suggests that similar success for other DS-related disruptions of brain growth, such as occurs in the hippocampus, could lead to additional treatments - perhaps prenatally - that restore memory and the ability to orient oneself in space.

DS is caused by an extra chromosome 21, a condition called trisomy - a third copy of a chromosome in addition to the normal two copies. Children with DS have a variety of abnormalities, such as slowed growth, abnormal facial features and mental retardation. The brain is always small and has a greatly reduced number of neurons.


A report on the Hopkins work with trisomic mice, led by Roger H. Reeves, Ph.D., professor in the Department of Physiology and the McKusick-Nathans Institute for Genetic Medicine at Hopkins, appears in the January 24 issue of the Proceedings of the National Academy of Sciences (PNAS).

Reeves and his team used an animal model of DS called the Ts65Dn trisomic mouse to show that pre-nerve cells called granule cell precursors (GCP) fail to grow correctly in response to stimulation by a natural growth-triggering protein. This protein, called Sonic hedgehog (Shh), normally activates the so-called Hedgehog pathway of signals in these cells. These signals stimulate mitosis (cell division) and multiplication of the cells in the growing, newborn brain, according to the researchers.

The GCP originate near the surface of the cerebellum and migrate deeper into the brain to form the internal granule layer (IGL), the researchers note. Therefore, the team studied the growth of the cerebellum in Ts65Dn trisomic mice at seven time points -- beginning at birth - to determine when GCP abnormalities first occurred. The IGL was similar in both normal and Ts65Dn mice at birth, but was significantly reduced in the trisomic mice by day six after birth.

Furthermore, the researchers found that the reduced number of GCP in these mice compared to normal mice was not due to cell death; rather, there were 21 percent fewer GCP undergoing cell division in Ts65Dn mice. This suggested that stimulating these cells might restore normal numbers of GCP, according to Reeves.

The Hopkins team then showed in test-tube experiments that GCP from the brains of Ts65Dn mice had a significantly lower response to increasing concentrations of a potent form of Shh called ShhNp. That is, increasing concentrations of ShhNp triggered increasing rates of mitosis. Despite their lower response, trisomic cells did show a dose response with increasing ShhNp concentrations.

"The fact that trisomic GCP responded to stimulation of their Hedgehog pathway even in a reduced way is significant," says Reeves, the senior author of the PNAS paper. "It suggested that these cells could be stimulated to reach normal levels of cell division by artificially increasing their exposure to Hedgehog growth factor."

Based on this initial discovery, the team injected into newborn Ts65Dn mice a molecule that stimulates the Hedgehog pathway to trigger cell growth. Treatment of the trisomic mice with this molecule, called SAG 1.1, restored both the numbers of GCP and the number of GCP cells undergoing mitosis to levels seen in normal mice by six days after birth.

"The normal mouse cerebellum attains about a third of its adult size in the first week after birth," says Randall J. Roper, Ph.D. "This is the time during which SAG 1.1 treatment of Ts65Dn restored GCP populations and the rate of mitosis of those cells," he adds. "However, further research is needed to determine if it’s possible to reverse the effects of trisomy in other parts of the DS mouse." Roper is a postdoctoral fellow in the laboratory of Reeves and a co-first author of the PNAS paper.

Gary Stephenson | EurekAlert!
Further information:
http://www.jhmi.edu
http://www.hopkinsmedicine.org/mediaII/RSSinstructions.html

More articles from Life Sciences:

nachricht How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>